Engineering placenta‐like organoids containing endogenous vascular cells from human‐induced pluripotent stem cells

Abstract

The placenta is an essential organ that maintains the health of both the fetus and its mother. Understanding the development of human placenta has been hindered by the limitations of existing animal models and monolayer cell cultures. Models that can recapitulate the essential aspects of human placental multicellular components and vasculature are still lacking. Herein, we presented a new strategy to establish placenta‐like organoids with vascular‐like structures from human‐induced pluripotent stem cells in a defined three‐dimensional (3D) culture system. The resulting placenta‐like tissue resembles first‐trimester human placental development in terms of complex placental components and secretory function. The multicellular tissue was characterized by the inclusion of trophoblasts (cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, and other endogenous vascular cells), which were identified by immunofluorescence, flow cytometry analyses, real‐time quantitative reverse transcription polymerase chain reaction and single‐cell RNA‐seq. Moreover, the 3D tissue was able to secrete the placenta‐specific hormone human chorionic gonadotropin β (hCG‐β) and vascular endothelial growth factor A (VEGFA). The tissue responded to the inflammatory factor tumor necrosis factor‐α (TNF‐α) and VEGF receptor inhibitors. This new model system can represent the major features of placental cellular components, and function, which have not been realized in 2D monolayer cultures. The developed tissue system might open new avenues for studying normal early human placental development and its disease states.

Human organoids-on-chips for biomedical research and applications

“…Recent advances in OrgOCs technology suggest various methods to tackle this problem using microengineered culture devices. A series of OrgOCs with microwell structure provides an instructive cue to guide the formation of HOs with uniform size and reduced stochasticity and variability, potentially reducing the unreliability of experimental results caused by heterogeneity 30 , 90 , 114 , 132 . Considering the uniformed size, controllability and modularity, this strategy is adjustable for size-based selection and also integrate into other systems for improved homogeneity of the organoid populations.…”

“…Usually, vascularized organoids can be generated containing endogenous vascular cells by adding indispensable growth factors (e.g., VEGFA) during induction stages 30 , 33 , 126 , 162 , 211 . Qin's group presented a novel strategy to engineer placenta-like organoids containing endogenous vascular cells (endothelial cells and pericytes) from hiPSCs on micropillar chips (Figure 3 A) 30 .…”

Establishment of the fetal-maternal interface: developmental events in human implantation and placentation

“…Human CTB 3D-organoid (CTB-ORG) cultures have recently been generated from purified first-trimester CTB preparations ( Haider et al, 2018 ; Cui et al, 2023 ; Dietrich et al, 2023 ). The established 3D organoids, which resembles the human placenta’s original structure and physiology, can maintain long-term self-renewal and expansion under specific culture conditions ( Haider et al, 2018 ; Dietrich et al, 2023 ).…”

Establishment of a new equation to estimate gestational age in female dogs

“…The placenta has been extensively studied in several countries and mammalian species, in addition to humans. There have been studies in Denmark (Lyderik et al, 2023), the United States (Cary et al, 2023; Fedorka & Troedson, 2023; Van Heule et al, 2023), New Zealand (Mccoard et al, 2023), Egypt (Hashem et al, 2023), Brazil (Farias et al, 2023), China (Cui et al, 2022) and Canada (Fuselier et al, 2023). The placenta is a transitory organ eliminated during childbirth and can be collected without risk to the mother and fetus after birth.…”